Kynurenine pathway (KP)

The kynurenine pathway is the principal metabolic route for tryptophan degradation in humans and many other organisms, leading to the synthesis of NAD+ and a variety of biologically active metabolites. It is highly conserved and plays critical roles in energy metabolism, neuronal health, immune modulation, and disease pathogenesis. Dysregulation is implicated in cancer (via immune suppression and tumor growth), neurological disorders (by shifting the balance of neurotoxic and neuroprotective metabolites), cardiovascular diseases, psychiatric illnesses, and chronic inflammation. Therapeutic intervention primarily targets key enzymes to modulate the pathway's impact on disease, utilizing enzyme inhibitors and modulators to restore metabolite homeostasis. Note: The "kynurenine pathway" is not a single molecule, receptor, or protein target but rather a series of interconnected metabolic steps involving multiple enzymes and metabolites. Most drug development focuses on the pathway's enzymes or key metabolites rather than the pathway as a whole. The pathway is nonetheless considered a unified therapeutic target in translational research and drug discovery.

Other names

Tryptophan-kynurenine pathwayKP

Inhibition of key enzymes (IDO, TDO, KMO) reduces the production of immunosuppressive or neurotoxic metabolites, enhancing anti-tumor immunity or neuroprotection Modulation of metabolite balance to favor neuroprotective products (e.g., boosting kynurenic acid, reducing quinolinic acid) Enhancement of immune cell function by reducing kynurenine and related immunosuppressive effects within the tumor microenvironment